The transcription factor HIF (hypoxia inducible factor) system is a key regulator of responses to hypoxia, occupying a central position in oxygen homeostasis in a wide range of organisms (1). A large number of transcriptional targets have been identified, with critical roles in angiogenesis, erythropoiesis, energy metabolism, inflammation, vasomotor function, and apoptotic/proliferative responses (1). The system is essential for normal development (2, 3), and plays a key role in pathophysiological responses to ischaemia/hypoxia (1). HIF is also important in cancer, in which it is commonly upregulated, and has major effects on tumour growth and angiogenesis (1). The HIF DNA binding complex consists of a heterodimer of α and β subunits (4). Regulation by oxygen occurs through hydroxylation of the α-subunits, which are rapidly destroyed by the proteasome in oxygenated cells (5, 6, 7). This involves binding of HIF-α subunits by the von Hippel-Lindau tumour suppressor protein (pVHL) (8), with pVHL acting as the, or part of the, recognition component for a ubiquitin ligase that promotes ubiquitin dependent proteolysis through interaction with a specific sequence or sequences in HIF-α-subunits (11, 12, 13, 14). In hypoxia, this process is suppressed, so stabilizing HIF-α and permitting transcriptional activation via the HIFα-β.